CAS No. 29232-93-7
The chemical 2-(diethylamino)-6-methylpyrimidin-4-ol/one is a metabolite of the organophosphorus insecticide pirimiphos-methyl, which has limited applications for control of beetles, weevils, and moths on stored grain products such as corn, sorghum, and seed. It has a lesser use as a cattle ear tag application to control flies. Pirimiphos-methyl is not registered for residential use in the United States. It easily hydrolyzes in the environment to 2-(diethylamino)-6-methylpyrimidine and other breakdown products, and it is not considered persistent. Though considered moderately-to-highly toxic in birds, fish, and aquatic invertebrates, occurrence of such toxicity is mitigated by its rapid degradation and its use in closed storage systems.
In the general population, infrequent dietary exposure to pirimiphos-methyl residues may occur from ingestion of food products containing stored corn or other treated grain (FDA, 2003). Estimated intakes from diet and water have not exceeded recommended intake limits (U.S. EPA, 2006). In animal studies, pirimiphos-methyl is rapidly absorbed and metabolized to 12 metabolites, which are mainly excreted in the urine (IPCS, 1992). Once absorbed, phosphorothioates such as pirimiphos-methyl are metabolically activated to the "oxon" form which has greater toxicity than the parent insecticide. Metabolic hydrolysis leads to the formation of 2-(diethylamino)-6-methylpyrimidin-4-ol/one, dialkyl phosphate metabolites (see section titled "Organophosphorus Insecticides: Dialkyl Phosphate Metabolites"), and other metabolites. In addition to being a human metabolite of pirimiphos-methyl in the body, 2-(diethylamino)-6-methylpyrimidin-4-ol/one can also occur in the environment. Thus, the detection of 2-(diethylamino)-6-methylpyrimidin-4-ol/one may also reflect exposure to the environmental degradate.
Human health effects from pirimiphos-methyl at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Pirimiphos-methyl has low acute toxicity in animal studies. At high doses, pirimiphos-methyl and other organophosphorus insecticides share a mechanism of toxicity: inhibition of the activity of acetylcholinesterase enzymes in the nervous system, resulting in excess acetylcholine at nerve terminals, and producing acute symptoms such as nausea, vomiting, cholinergic effects, weakness, paralysis, and seizures. The metabolite 2-(diethylamino)-6-methylpyrimidin-4-ol/one does not inhibit acetylcholinesterase enzymes. Toxic effects below doses that cause inhibition of acetylcholinesterase are unknown. Pirimiphos-methyl is not considered mutagenic, teratogenic, or known to cause delayed neurotoxicity, or reproductive toxicity (IPCS, 1992; U.S. EPA, 2006). Additional information about pesticides is available from U.S. EPA at: http://www.epa.gov/pesticides/.
Urinary levels of 2-(diethylamino)-6-methylpyrimidin-4-ol/one reflect recent exposure. In the U.S. subsample of NHANES 2001–2002, most of the urinary measurements of 2-(diethylamino)-6-methylpyrimidin-4-ol/one were below the limit of detection, although the 95th percentile was characterized at 0.47 µg/L for the total population (CDC, 2005). In a nonrandom sample of 140 urine specimens obtained from adults and children in the United States, Olsson et al. (2003) detected 2-(diethylamino)-6-methylpyrimidin-4-ol/one in 7.1% of the sampled population.
Finding a measurable amount of 2-(diethylamino)-6-methylpyrimidin-4-ol/one in urine does not mean that the level will result in an adverse health effect. Biomonitoring studies of 2-(diethylamino)-6-methylpyrimidin-4-ol/one provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of pirimiphos-methyl than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.
Centers for Disease Control and Prevention (CDC). Third National Report on Human Exposure to Environmental Chemicals. Atlanta (GA). 2005. 4/7/09
Food and Drug Administration (FDA). Total Diet Study: Summary of Residues Found Ordered by Pesticide, Market Baskets 91-3-01-4. June 2003. Available at URL: http://www.fda.gov/downloads/Food/FoodSafety/FoodContaminantsAdulteration/TotalDietStudy/UCM184304.pdf. 4/7/09
International Programme on Chemical Safety-INCHEM (IPCS). Pesticides residues in food: 1992 evaluations Part II Toxicology. 850. Pirimiphos-methyl. Available at URL: http://www.inchem.org/documents/jmpr/jmpmono/v92pr16.htm. 4/7/09
Olsson AO, Nguyen JV, Sadowski MA, Barr DB. A liquid chromatography/electrospray ionization tandem mass spectrometry method for quantification of specific organophosphorus pesticide biomarkers in human urine. Anal Bioanal Chem 2003;376(6):808-815.
U.S. Environmental Protection Agency (U.S. EPA). Finalization of interim registration eligibility decision for pirimiphos-methyl. Case No. 2535. July 2006. Available at URL: http://www.epa.gov/oppsrrd1/REDs/pirimiphos-methyl_ired.pdf. 1/14/09